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Colonization is the presence of bacteria which are NOT causing disease.

Infection is The presence of bacteria which ARE causing disease, often found in normally sterile
location(s).

What is the difference between Colonization and Infection?

mouth and oropharynx (including sputum)
GI tract
skin

Sites that are normally NON-STERILE are what?

Mouth anaerobes (normal mouth flora)
Gut anaerobes (normal gut flora)

What bacteria would you normally find in the mouth and GI tract?

Staphylococcus
Streptococcus

What bacteria would you normally find on the skin?

Blood
CSF
Urine

What are the sites that are commonly STERILE in the body?

Staphylococcus and Streptococcus from skin goes into the blood...

Gut anaerobes from GI tract goes into blood after sex (tearing of anal wall, for example)...

What bacteria can be found in the blood?

Otitis media bugs (S. pneumoniae, H. influenzae)
because Ear Canal close to BBB...

Staph and Strep from skin, goes into blood, then to CSF...

What bacteria can be found in the CSF?

Gut bugs - Gram negatives
Staph and Strep

What bacteria can be found in the urine?

Contaminant

Mouth anaerobes cannot survive in the lungs, so the sample taken must have been contaminated.

You did a bronchial lavage culture. The report came back as "mouth anaerobes".

Is this colonization, infection, or contaminant?

Infection

Streptococcus pneumoniae typically not found in the mouth.

You did a bronchial lavage culture. The report came back as "Streptococcus pneumoniae".

Is this colonization, infection, or contaminant?

Susceptibility testing

Infection of hospitalized patients or infections requiring hospitalizations: What kind of test is first ordered?

A narrow spectrum antibiotic is used to treat the patients while adjustments are made to the medication accordingly.

Narrow spectrum used to prevent resistance and superinfection.

After getting results from susceptibility testing, what happens?

A test which uses antibiotic-impregnated wafers to test whether particular bacteria are susceptible to specific antibiotics.

A known quantity of bacteria are grown on agar plates in the presence of thin wafers containing relevant antibiotics. If the bacteria are susceptible to a particular antibiotic, an area of clearing surrounds the wafer where bacteria are not capable of growing (called a zone of inhibition).

Along with rate of antibiotic diffusion, it's used to estimate the bacteria's sensitivity to that particular antibiotic.

What is the Kirby-Bauer Test?

Correlates with smaller MIC

In general, how do larger zones in a Kirby-Bauer test correlate with MIC?

An agar diffusion method used to determine whether or not a specific strain of bacterium or fungus is susceptible to the action of a specific antibiotic.

This is most commonly used in the setting of medicine, where a doctor treating an infected patient seeks guidance on what concentration of antibiotic is suitable.

The Etest utilises a rectangular strip that has been impregnated with the drug to be studied. A lawn of bacteria is spread and grown on an agar plate, and the Etest strip is laid on top; the drug diffuses out into the agar, producing an exponential gradient of the drug to be tested. There is an exponential scale printed on the strip. After 24 hours of incubation, an elliptical zone of inhibition is produced and the point at which the ellipse meets the strip gives a reading for the minimum inhibitory concentration (MIC) of the drug.

What is the E Test?

Minimum inhibitory concentration (MIC)

The lowest concentration of the antibiotic that
results in inhibition of visible growth under
standard conditions.

What is MIC?

Minimum bactericidal concentration (MBC)

The lowest concentration of the antibiotic that kills
99.9% of the original inoculum in a given time.

What is MBC?

PREVENT infection

Antibiotic selected in prophylactic therapy is used to do what?

HIV/AIDS

Immunocompromised...
...Organ transplant
...Long-term steroid use

Recurrent UTIs

What disease states or conditions do we utilize
prophylactic therapies and WHY?

A SUSPECTED pathogen as you await for culture results

(BROAD SPECTRUM ANTIBIOTIC USED)

Antibiotic selected in Empiric therapy is used to treat what?

A KNOWN pathogen once culture and sensitivity results are known

(NARROW SPECTRUM ANTIBIOTIC USED)

Antibiotic selected in Specific therapy is used to treat what?

The highest concentration of antibiotics that can be safely attained in the blood using the recommended dosing regimen.

What is the Breakpoint MIC?

MIC of organism is LESS THAN breakpoint MIC

Yes.

How does the MIC of the infecting organism compare to the Breakpoint MIC if the organism is SENSITIVE to the antibiotic?

Can you use this Antibiotic?

MIC of organism EQUALS Breakpoint MIC

It's okay to use ONLY if there is no other option.

How does the MIC of the infecting organism compare to the Breakpoint MIC if the organism has INTERMEDIATE SENSITIVITY to the antibiotic?

Can you use this Antibiotic?

MIC of organism is GREATER THAN breakpoint MIC

Absolutely NOT.

How does the MIC of the infecting organism compare to the Breakpoint MIC if the organism is RESISTANT to the antibiotic?

Can you use this Antibiotic?

Dose can be toxic to the patient.

Dose may cause adverse effects in the patient.

What can happen if the drug dose is greater than the Breakpoint MIC?

Sensitive

Ampicillin
Organism MIC = 0.1
Breakpoint MIC = 8

Sensitive, Intermediate Sensitivity, or Resistant?

Sensitive

Not "I" because the fraction is TMP/SMX.

For TMP, it's 1 vs. 2.
For SMX, it's 19 vs. 38.

So, for both numerator and denominator, the Breakpoint MIC is higher, so Sensitive.

TMP/SMX
Organism MIC = 1/19
Breakpoint MIC = 2/38

Sensitive, Intermediate Sensitivity, or Resistant?

Intermediate

Ceftazidime
Organism MIC = 16
Breakpoint MIC = 16

Sensitive, Intermediate Sensitivity, or Resistant?

Resistant

Aztreonam
Organism MIC = 64
Breakpoint MIC = 16

Sensitive, Intermediate Sensitivity, or Resistant?

Must achieve MIC at site of infection.

Antibiotics that work via time-dependent killing must do what in order to be effective?

Peak levels determine adequacy of treatment

Trough levels predicts toxicity

When using antibiotics that work via concentration-dependent killing, peak and trough levels determine what?

Can lead to bacterial growth and/or resistance

What can happen if the drug level is less than the organism's MIC?

Can cause adverse effects

For certain antibiotics, what can happen if you give a patient another dose before the old dose is cleared from the body?

Absorption (bioavailability)
Distribution

What two factors determine the dose, route and frequency of administration of antibiotic?

The antibiotic must be able to reach the site of infection. If it can't reach the infection site, it won't be able to act.

In order for any antibiotic to work, what must first happen?

During the dosing interval, time-dependent drugs are effective because of the extensive amount of time the antibiotics bind to the microorganism while their their concentration exceeds the MIC for the microorganism.

Hence, these antibiotics are referred to as time-dependent antibiotics. For time-dependent drugs, the pharmacodynamic parameter can be simplified to the time that serum concentrations remain above the MIC during the dosing interval (t>MIC).

Describe the concept of time-dependent killing and time-dependent antibiotics.

Concentration-dependent drugs have high concentrations at the binding site which eradicates the microorganism.

For concentration-dependent agents, the pharmacodynamic parameter can be simplified as a peak/MIC ratio.

Describe the concept of concentration-dependent killing and concentration-dependent antibiotics.

Cell-wall active agents...
...Βeta-lactam antibiotics
...Vancomycin

What kind of antibiotics works via time-dependent killing?

Persistent suppression of bacterial growth after a brief exposure (1 or 2 hours) of bacteria to an antibiotic even in the absence of host defense mechanisms. Factors that affect the duration of the post antibiotic effect include duration of antibiotic exposure, bacterial species, culture medium and class of antibiotic.

What is the post-antibiotic effect?

the greater the antibiotic effect

- Aminoglycosides
- Fluoroquinolones

For antibiotics that work via concentration-dependent killing, the higher the achieved concentration vs. MIC (Peak/MIC > 10), the what?

This is true for what antibiotics?

The greater the antibiotic effect

-Fluoroquinolones
-Β-lactam antibiotics
-Vancomycin

For antibiotics that work via concentration-dependent killing, the greater the AUC/MIC (>125), the what?

This is true for what antibiotics?

-thromycin

Macrolide names end in what?

-floxacin

Fluoroquinolone names end in what?

-amicin/ -amycin

Exceptions:
Amikacin (aminoglycoside)
Vancomycin (not aminoglycoside)
Daptomycin (not aminoglycoside)
Clindamycin (not aminoglycoside)

Aminoglycoside names end in what?

What are the exceptions?

- CSF
- Lung
- Bone
- Heart
- Abscesses

What sites are the most difficult to get antibiotics to?

-Lack of antibiotic penetration
-pH inactivation of antibiotic (<6)
-Enzyme inactivation

Why is it difficult to get antibiotics to penetrate abscesses?

Above - Clindamycin

Below - Metronidazole

Which antibiotics treat abscesses above and below the diaphragm, respectively?

-Hypotension (decrease blood (and therefore drugs) to organs)
-Ileus (Changes amount and consistency of drug absorption)
-Colitis (Changes amount and consistency of drug absorption)
-Bowel ischemia (Changes amount and consistency of drug absorption)
-Change in gastric pH (Changes the rate at which a drug is absorbed)

Identify conditions that would impair the bioavailability of an intravenous or oral medication. Give a brief explanation as to why this is.

-Cirrhosis
-CHF
-Pregnancy

These are all conditions that increase the amount of fluid in a person. Drugs that require dosing based on volume distribution will need to have dosing adjusted.

Identify conditions that would increase the volume of distribution, requiring larger doses to be given. Give a brief explanation as to why this is.

...

Study the image.

Endocarditis
Meningitis

Bacteriocidal used when the condition is more severe or if there is greater risk of complications.

Which of the following medical conditions should you use a bacteriCIDAL agent? Check all that apply.
-Endocarditis
-Urinary tract infection
-Strep throat
-Meningitis

Amoxicillin
Ciprofloxacin
Most oral therapy.

NEVER in children.

Give an example of an antibiotic with a recommended dose that does not take into account pharmacokinetic principles (is the same for everyone).

For children, dosing are ALWAYS determined based on mg of drug per kg of body weight.

What is the dosing rule when it comes to children?

-Good oral bioavailability
-DOES NOT have narrow therapeutic window
-No adverse reactions associated with peaks and troughs

For drugs that have a recommended dose and does not take into account pharmacokinetic principles, what are the characteristics that allow dosing for almost every person to be the same?

Vancomycin
Aminoglycoside
Any agents with narrow therapeutic windows

Give an example of an antibiotic that requires pharmacokinetic principles to determine the dose.

-If they are based on volume and distribution
-If they require renal dosing adjustments
-The site of infection
-If there are toxic doses that necessitates the monitoring of troughs and peaks.

For drugs that require pharmacokinetic principles to determine the dose, what are the characteristics of this drug that causes dosing for almost every person be different?

N-acetylglucosamine

N-acteylmuramic acid

The building blocks of bacterial cell walls consist of what two amino sugars?

Beta-1,4-glycosidic linkages

In the bacterial cell wall, N-acetylglucosamine and N-acteylmuramic acid are connected via what bond?

Each N-acetylmuramic acid has 5-AA peptide attach to it. The 5-AA peptide of adjacent N-acetylmuramic acids bind one another (forming peptide bonds).

This reaction is catalyzed by TRANSPEPTIDASE.

Describe the peptide bonds formed between the building blocks of bacterial cell walls.

What enzyme catalyzes the formation of this bond?

Transglycosylase

What enzyme catalyzes the formation of the Beta-1,4-glycosidic linkages between N-acetylglucosamine and N-acteylmuramic acid?

Inhibits cell wall synthesis

What is the Mechanism of Action (MOA) of Penicillin?

Inhibits cell wall synthesis

What is the Mechanism of Action (MOA) of Cephalosporins?

Inhibits cell wall synthesis

Similar to Vancomycin.

Vancomycin: Inhibits the formation of peptidoglycan, so cross-linking of peptidoglycan cannot occur. It does this by mimicking the D-Ala-D-Ala dipeptide of peptidoglycan and getting incorporated into the cell wall. This leads to osmotic fragility and cell lysis.

What is the Mechanism of Action (MOA) of Bacitracin?

Injury to plasma membrane

What is the Mechanism of Action (MOA) of Polymixin B?

Inhibits cell wall synthesis

Inhibits the formation of peptidoglycan, so cross-linking of peptidoglycan cannot occur. It does this by mimicking the D-Ala-D-Ala dipeptide of peptidoglycan and getting incorporated into the cell wall. This leads to osmotic fragility and cell lysis.

What is the Mechanism of Action (MOA) of Vancomycin?

Inhibit protein synthesis

Binds to 50S subunit of bacterial ribosome. Prevents translocation - movement of ribosome along the mRNA.

What is the Mechanism of Action (MOA) of Macrolide?

Inhibit protein synthesis

Changes shape of 30S portion of bacterial ribosome by binding irreversibly to it. This causes code on mRNA to be read incorrectly.

What is the Mechanism of Action (MOA) of Aminoglycoside?

Inhibits synthesis of essential metabolites

Blocks synthesis of Dihydropteroate

What is the Mechanism of Action (MOA) of Sulfonamide?

Inhibits synthesis of essential metabolites

Blocks action of Dihydrofolate reductase, so Tetrahydrofolic acid not formed!

What is the Mechanism of Action (MOA) of Trimethoprim (TMP)?

Inhibit protein synthesis

Binds irreversibly to 30S ribosomal subunit and interferes with attachment of tRNA to mRNA complex.

What is the Mechanism of Action (MOA) of Tetracycline?

Inhibits DNA/RNA replication or transcription

What is the Mechanism of Action (MOA) of Quinolones?

Inhibit protein synthesis

Inhibits bacterial protein synthesis by binding to the
50S ribosomal subunit (NOT present in human cells) and blocking translocation reactions

What is the Mechanism of Action (MOA) of Clindamycin?

Inhibit protein synthesis

Inhibits protein synthesis by binding to a receptor on 23S ribosomal RNA (part of the 50S subunit)

What is the Mechanism of Action (MOA) of Linezolid?

Inhibit protein synthesis

Dalfopristin:
Blocks an early step in protein synthesis by forming a bond with a ribosome to prevent elongation of peptide chain.

What is the Mechanism of Action (MOA) of Dalfopristin?

Inhibit protein synthesis

Quinupristin:
Blocks a later step in protein synthesis by preventing
the extension of peptide chains.

What is the Mechanism of Action (MOA) of Quinopristin?

Inhibits cell wall synthesis

What is the Mechanism of Action (MOA) of Monobactams?

Inhibits RNA replication or transcription

Binds to the Beta subunit of bacterial DNA-dependent RNA polymerase. This inhibits RNA
synthesis.

What is the Mechanism of Action (MOA) of Rifampin?

Inhibits cell wall synthesis

What is the Mechanism of Action (MOA) of Carbapenems?

When 2 or more antibiotics, with different MOAs, working together to allow a dosage reduction and/or faster and enhanced drug effect on organism.

What is synergism?

When one antibiotic interferes with the effects of another antibiotic.

What is antibiotic antagonism?

The more sites targeted on a microorganism, the greater the likelihood that it will get eradicated.

Why do you want to use antibiotics with different MOAs to achieve synergy?

Beta lactams

Should not be used together because they will compete for the same binding sites. This will eventually lead to resistance.

Name antibiotics that cannot be used together or infused with one another.

b) Penicillin and aminoglycoside

a) Wrong. They have the same MOAs.
c) Wrong. Have different MOAs but act on different bacteria.
d) Wrong. Target different subunit of the ribosome, so spectrum of activity is not the same.

What antibiotic classes, when used together, would be synergistic in treating an infection?
a) Penicillin and cephalosporin
b) Penicillin and aminoglycoside
c) Rifampin and quinolone
d) Erythromycin and tetracycline

A) Synergism (left-most)
B) Antagonism (middle)
C) Neither (right-most) - The graph of the combined effects of E and F indicates that the combined effects is still just as good as F alone. E did not bring it down.

Exaggerated, inappropriate, or prolonged immune
responses that cause damage to otherwise normal tissue.

Drugs can cause an allergic reaction. What is allergy?

An adverse side effect that is NOT immune- mediated.

Continuation of therapy may or may not be effected

Examples:
- Upset stomach
- Light-headedness
- Dry mouth
- Cough

What is drug sensitivity?

Should you stop treatment if a patient has drug sensitivity?

Give examples of drug sensitivities.

All other Beta-lactams - Because they all have the Beta-lactam ring structure.

If the patient has a penicillin allergy, what other class(es) would the patient potentially have a reaction to? Explain your reasoning.

Inhibit Cell Wall Synthesis:

-Bind to Penicillin-Binding Proteins (PBPs) located
on the inner surface of the cell wall.
-Interferes with cross-linking of peptidoglycan
-Osmotic fragility and cell lysis

How do Beta Lactams work?

Inhibitors of cell wall synthesis.

Vancomycin, Bacitracin, and Daptomycin are all what?

Beta lactam ring.

What are we looking at here?

The beta-lactam ring.

What site on a beta-lactam bind penicillin binding protein and is also targeted by beta-lactamases?

Bactericidal

Beta lactams are bacteriocidal or bacteriostatic?

time-dependent

Are beta-lactams time-dependent killers or concentration-dependent killers?

If the active form is unchanged via excretion in the kidneys, then it can be used to treat UTIs.

Beta lactams are excreted unchanged via the kidneys. How can this be beneficial?

Beta-lactams

Infusion is NOT the same as using together at the same time.

What family of antibiotics should NOT be infused with any other antibiotic (even though they can be used simultaneously with some other antibiotic)?

The penicillin will inactivate the aminoglycoside.

So, you will need to infuse penicillin first, then aminoglycoside second.

What will happen if you infuse penicillins with aminoglycosides?

True

True or False?
ALL antibiotics can cause GI upset.

Sensitivity reaction

The GI upset caused by antibiotics is considered an allergic reaction of a sensitivity reaction?

Fever, urticaria, angioedema, arthralgia

What are the symptoms of Interstitial nephritis?

Hemolytic anemia

Coomb's Test is used to test for what?

-Interstitial nephritis
-Decreased platelet aggregation
-Hemolysis
-Leukopenia, neutropenia, thrombocytopenia
with prolonged therapy (> 2 weeks)
-Neurologic complaints (w/ penicillins and
carbapenems)

What are the adverse effects of Beta-lactams?

It will mutate and produce Beta-lactamase (resistance)

What will happen to an organism if you continually expose it to Beta-lactams?

-Staphylococci
-Haemophilus influenzae
-Bacteriodes fragilis
-Klebsiella species

Name 4 common bacteria that produce β-lactamases.

Beta-lactamase Enzymes

The leading cause of resistance to Beta-lactam antibiotics is what?

A Beta-Lactamase Inhibitor is added.

Most penicillins are inactivated by bacteria that produce Beta-lactamase unless what happens?

Clavulanic acid
Sulbactam
Tazobactam

What are the compounds typically added to beta-lactams to confer resistance to beta-lactamase?

-Anti-staph penicillins (Naficillin)
-ALL cephalosporins (but not all are active against
staph)
-Carbapenems
-Vancomycin

Which Beta-lactams are structurally resistant to Beta-lactamase?

That the resistance is not due to beta lactamase.

If one of the structurally resistant (to beta lactamase) beta lactams are reported as being resistant to a particular bacteria, you know what for certain?

mecA

What gene confers classical methicillin resistance to certain strains of bacteria?

Extended spectrum (3rd generation) cephalosporins and monobactams.

Extended-Spectrum Beta-Lactamases (ESBLs) are enzymes that cause resistance to what antibiotics?

Only the Carbapenem and 2nd generation cephalosporin will work.

The bacteria will have resistance to the monobactam (thanks to the ESBL enzyme).

A person is infected with a bacteria that is strengthened with ESBL enzymes. Your colleague decides to treat him with either a 2nd generation cephalosporin, monobactam, or a carbapenem, and asks you which one will work.

What would you tell him?

-Penicillins
-3rd generation cephalosporins
-aztreonam

If you detect ESBL in a patient, you should avoid using what antibiotics?

Ampicillin and Amoxicillin

What are the aminopenicillins?

Beta-Lactamase resistant penicillins

Nafcillin and Methicillin are both what?

-Na+ or K+ overload with IV formulations of penicillins

-Beta-lactamase inhibitors increase incidence of
diarrhea

-If patient has VIRAL infection or on ALLOPURINOL, increased incidence of rash (only for Amoxicillin and Ampicillin)

What are three adverse effects associated with penicillins?

Overgrowth of Candida pseudomembranous colitis, which is secondary to C. difficile infection.

Over exposure to antibiotics can cause something associated with C. difficile. What is it?

HT or CHF

Because patients may retain more fluid
secondary to increase in sodium leading to fluid
overload (exacerbating the condition).

What disease states do you need to monitor if a patient is going to receive IV Penicillin?

Ampicillin or Amoxicillin

A TOXIC REACTION can occur (NOT allergy to penicillin, but actually a TOXIC reaction to these two specific drugs).

Symptoms:
Macular or maculopapular erythematous, pruritic rash on face, neck, trunk, and extremities

Patients with mononucleosis (viral infection) may present with a strept throat infection. What should you NEVER give these patients?

Supportive care

No.

Joanne is a 15 year-old female diagnosed with mononucleosis. She has no known allergies. What treatment do you recommend?

Does Joanne need antibiotic therapy?

Yes, Penicillin.

Amoxicillin and Ampicillin.

Paula is a 15 year-old female diagnosed with mononucleosis and strep throat. She has no known allergies.

Does Paula need antibiotic therapy? If yes, what therapy?

What medication(s) can you NOT give Paula?

No.

Are upset stomach and/or nausea/vomiting symptoms of a true allergy to penicillin?

Range from mild rash to anaphylaxis.

Serum sickness, fever, urticaria, angioedema, and
arthralgia.

In about 3-10% of the population, allergy to penicillin is in the form of hypersensitivity reaction. What are the symptoms associated with it?

Any beta-lactam - though it is less with monobactams.

If a patient has true penicillin allergy, you should avoid giving him/her what?

Higher if given via IV

Would you expect higher or lower incidence of penicillin allergy-derived hypersensitivity reaction when the drug is administered via IV as opposed to other routes?

Cephalosporin's incorporate themselves into the
cell wall by binding to Penicillin Binding Protein (PBP).

During replication, daughter cells are unable to
"close" where the cell wall was in contact with the
cephalosporin leading to cell death.

What is the mechanism of action of Cephalosporins?

Same as those for penicillins and other beta-lactams.

What are the adverse effects of cephalosporins?

AVOID ALCOHOL!!!

Can cause disulfiram-like reaction secondary to MTT group blocking alcohol metabolism

What should you warn patients who are about to be placed on a Cefotetan treatment regimen?

Abdominal pain and nausea/vomiting, especially after fatty meals. This can lead to gallstone formation.

Ceftriaxone can cause biliary sludging. What symptoms are associated with this?

False. Not all of them.

True or False?
All cephalosporins have activity against Staphylococcus (MRSA) or gram positive infections.

ONLY GRAM-NEGATIVES!!!

Klebsiella, E. coli, Enterobacteriaceae (Salmonella
and Proteus), Pseudomonas (PSA)

What common bacteria produce ESBLs?

1st generation = more gram + activity

2nd generation = maintains some gram +, but gains
gram -

3rd generation = still has gram +, but increased gram -

4th generation = maintains gram - activity, but regains gram +

5th generation = "Advanced Generation" - advanced
gram + activity (MRSA, VISA, and VRSA), but little gram - activity

Describe each of the cephalosporin generation of antibiotics in terms of their effectiveness in treating gram-neg and gram-pos infections.

Cephalexin = PO

Cefazolin = IV

Between Cephalexin and Cefazolin, which one is PO and which one IV?

Gram(+) bacteria = Staph (MSSA, MSSE) and Strep
Also, active against most "E, P, K" (Gram(-))

Cephalexin and Cefazolin are active against what type of bacteria?

Enterococci

Cephalexin and Cefazolin are not active against what type of gram(+) bacteria?

Second - because they have poor CNS penetration

If you suspect meningitis or other CNS infection, what generation cephalosporin should you avoid? Why?

Sinusitis and otitis media

Cefuroxime (can be given via IV or PO) and Cefaclor (can be given via PO) are both 2nd generation antibiotics. They are good for treating what?

Abdominal infections or ischemic skin and soft tissue conditions.

Cefoxitin (given via IV) and Cefotetan (given via IV) are second generation cephalosporins. They are good for treating what?

-Third generation Cephalosporin.

-Best activity against penicillin resistant strains of bacteria.
-Streptococcus pneumoniae.
-Good gram(-) coverage

-Bad against Pseudomonas.

Ceftriaxone (given via IV) is what type of antibiotic? How is it administered?

It is best used for treating what? Not good against what strains?

Second generation cephalosporin. Given via IV.

What type of antibiotic is Cefotetan? How is it administered?

Yes.

Third generation = Good CNS penetration

Would you ever use a third generation cephalosporin to treat a CNS bacterial infection?

- Low molecular weight
- Non-ionized at physiological pH
- Highly lipid soluble (large Vd)
- Not extensively protein bound
- More ABX can cross if meninges are inflamed
- Not a p-glycoprotein substrate

What are the unique characteristics of those antibiotics that can penetrate the BBB (i.e. what allows the drug to penetrate the blood brain barrier)?

Only available in IV

Fourth generation cephalosporins can be administered via what route(s)?

Better action against gram (+) while retaining potency for gram (-)

How are 4th generation cephalosporins an improvement over the 3rd generation?

Effective =
- Skin/Soft tissue gram(+): MRSA, VISA, and VRSA
- Respiratory gram(-): M. catarrhalis and H. influenzae

Not Effective = Bacteria with ESBLs

5th generation cephalosporins are the "advanced generation" cephalosporins. They are active against what?

What are they NOT effective against?

First generation: Cefazolin

What generation Cephalosporin is typically given via IV to prevent pre- and post-operative incision site infection?

Carbapenems

What beta lactam group has the broadest spectrum of activity (compared to the other beta lactams)?

Pseudomonas (PSA) and Acinetobacter

What two family of antibiotics develops resistance quickly to Carbapenems?

Yes.

Yes.

Are carbapenems beta lactamase resistant?

Are they resistant against bacteria with ESBL?

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